The study aims to inform potential cost-effectiveness analysis of hypertension management in Vietnam by providing utilities and predictors of utilities in patients with hypertension.
Hypertensive ...patients up to 80 years old visiting the hospital were invited to participate in a survey using Quality Metric's Short-form 36v2TM translated into Vietnamese. Health-state utilities were estimated by applying a previously published algorithm.
The mean utility of the 691 patients interviewed was 0.73. Controlling for age, sex, blood pressure (BP) stage, and history of stroke, the utilities in older patients were lower than those in younger ones, and statistically significantly different between the extremes of youngest and oldest groups (p = 0.03). Utility in males was higher than in females (p = 0.002). As expected, patients with a history of stroke appeared to exhibit lower utilities than patients without such history, but the difference was not statistically significant (p = 0.73). Patients with more than three comorbidities did have lower utilities than patients without comorbidity (p = 0.01).
Health-state utilities found among hypertensive patients in Vietnam were similar to those found in other international studies. It is suggested that lower of health-state utilities exist among those patients who were older, female or had more than three comorbidities in comparison with respective reference groups. However, further research for confirmation is required. The data from this study provide a potential reference on health-state utilities of hypertensive patients in Vietnam as an input for future cost-effectiveness analysis of interventions. Also, it may serve as a reference for other similar populations, especially in the context of similar environments in low income countries.
Gaps in primary hyperparathyroidism diagnosis are well-documented. End-organ damage correlates with disease duration and often occurs before diagnosis. We hypothesize that opportunistic parathyroid ...gland assessment on routine CT could decrease existing diagnosis gaps. Our purpose is to assess for enlarged parathyroid glands on contrast-enhanced CT acquired prior to biochemical screening and subsequent development of related morbidity.
This retrospective study included consecutive patients with primary hyperparathyroidism undergoing parathyroidectomy with contrast-enhanced CT including the lower neck and upper chest acquired prior to biochemical screening. One neuroradiologist retrospectively evaluated all CTs for enlarged (estimated weight greater than 60 mg) parathyroid glands. Gold standard operative and pathology reports were correlated with CT findings, and medical records were reviewed for development of primary hyperparathyroidism-related comorbidities.
The sample comprised 38 patients (30 women, 8 men, median age 60 years) with 70 CTs of interest. The neuroradiologist identified 32 putative enlarged parathyroid glands (median estimated weight 307 mg) in 29 (76%) patients on CTs predating biochemical screening by a median of 30 months. Putative enlarged parathyroid glands on CT corresponded to pathologically proven parathyroid lesions in 26 (90%) patients. Of 26 patients with retrospectively identified pathologically proven parathyroid lesions, 12 (46%) developed at least 1 renal, bone, or neurocognitive comorbidity between CT and subsequent biochemical screening.
Enlarged parathyroid glands are frequently visible on routine CTs acquired years prior to primary hyperparathyroidism diagnosis. Biochemical screening based on enlarged glands could potentially prevent associated morbidity in almost half of such patients.
Fully differentiated pancreatic β cells are essential for normal glucose homeostasis in mammals. Dedifferentiation of these cells has been suggested to occur in type 2 diabetes, impairing insulin ...production. Since chronic fuel excess (“glucotoxicity”) is implicated in this process, we sought here to identify the potential roles in β‐cell identity of the tumor suppressor liver kinase B1 (LKB1/STK11) and the downstream fuel‐sensitive kinase, AMP‐activated protein kinase (AMPK). Highly β‐cell‐restricted deletion of each kinase in mice, using an Ins1‐controlled Cre, was therefore followed by physiological, morphometric, and massive parallel sequencing analysis. Loss of LKB1 strikingly (2.0‐12‐fold, E<0.01) increased the expression of subsets of hepatic (Alb, Iyd, Elovl2) and neuronal (Nptx2, Dlgap2, Cartpt, Pdyn) genes, enhancing glutamate signaling. These changes were partially recapitulated by the loss of AMPK, which also up‐regulated β‐cell “disallowed” genes (Slc16a1, Ldha, Mgst1, Pdgfra) 1.8‐ to 3.4‐fold (E<0.01). Correspondingly, targeted promoters were enriched for neuronal (Zfp206; P= 1.3×10‐33) and hypoxia‐regulated (HIF1; P= 2.5×10‐16) transcription factors. In summary, LKB1 and AMPK, through only partly overlapping mechanisms, maintain β‐cell identity by suppressing alternate pathways leading to neuronal, hepatic, and other characteristics. Selective targeting of these enzymes may provide a new approach to maintaining β‐cell function in some forms of diabetes.—Kone, M., Pullen, T. J., Sun, G., Ibberson, M., Martinez‐Sanchez, A., Sayers, S., Nguyen‐Tu, M.‐S., Kantor, C., Swisa, A., Dor, Y., Gorman, T., Ferrer, J., Thorens, B., Reimann, F., Gribble, F., McGinty, J. A., Chen, L., French, P. M., Birzele, F., Hildebrandt, T., Uphues, I., Rutter, G. A., LKB1 and AMPK differentially regulate pancreatic β‐cell identity. FASEB J. 28, 4972–4985 (2014). www.fasebj.org
•Using the FDA adverse event reporting system database, ETI and DILI reports were found to be significantly associated (p < 0.05) for all disproportionality measures (PRR, ROR, IC, EGBM, ...chi-squared).•The ROR for ETI-DILI is greater than that of ∼10 % of the “Most-DILI concern” drugs in the FDA DILIRank dataset.•ETI-DILI reports for people with cystic fibrosis were predominately male, in contrast to patient reports for other drugs and DILI.•“Hospitalization” was the second most common patient outcome for ETI-DILI after "other serious outcomes”.•Most people with cystic fibrosis experienced onset times within 3 months of initiation; however, several occurred prior to 3 months or beyond 1 year, indicating additional monitoring may be prudent.
The efficacy and safety of elexacaftor/tezacaftor/ivacaftor (ETI) have been established in prospective clinical trials. Liver function test elevations were observed in a greater proportion of patients receiving ETI compared with placebo; however, the relatively small number of patients and short duration of study preclude detection of rare but clinically significant associations with drug-induced liver injury (DILI). To address this gap, we assessed the real-world risk of DILI associated with ETI through data mining of the FDA adverse event reporting system (FAERS).
Disproportionality analyses were conducted on FAERS data from the fourth quarter of 2019 through the third quarter of 2022. Comparative patient demographics, onset time and outcomes for ETI-DILI were also obtained.
452 reports of DILI associated with ETI were found, representing 2.1 % of all adverse event reports for ETI. All disproportionality measures were significant for ETI-DILI at p < 0.05; the reporting odds ratio (ROR) (2.82) was comparable to that of drugs classified by FDA as “Most-DILI concern”. The most notable demographic finding was a male majority (5:4 male to female ratio) for ETI-DILI compared to a female majority (4:5 male to female ratio) for non ETI-DILI. Median ETI-DILI onset time was 50.5 days, and hospitalization was the second most common complication.
Using FAERS data, ETI was found to be disproportionately associated with DILI. Future research is needed to investigate the hepatotoxic mechanisms and assess potential mitigation strategies for ETI-induced hepatotoxicity.
Cytokine-based therapies for cancer have not achieved widespread clinical success because of inherent toxicities. Treatment for pancreatic cancer is limited by the dense stroma that surrounds tumors ...and by an immunosuppressive tumor microenvironment. To overcome these barriers, we developed constructs of single-domain antibodies (VHHs) against PD-L1 fused with IL-2 and IFNγ. Targeting cytokine delivery in this manner reduced pancreatic tumor burden by 50%, whereas cytokines fused to an irrelevant VHH, or blockade of PD-L1 alone, showed little effect. Targeted delivery of IL-2 increased the number of intratumoral CD8
T cells, whereas IFNγ reduced the number of CD11b
cells and skewed intratumoral macrophages toward the display of M1-like characteristics. Imaging of fluorescent VHH-IFNγ constructs, as well as transcriptional profiling, demonstrated targeting of IFNγ to the tumor microenvironment. Many tumors and tumor-infiltrating myeloid cells express PD-L1, rendering them potentially susceptible to this form of targeted immunotherapy.
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On the 26th of November 2021, the World Health Organization (WHO) designated the newly detected B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the Omicron Variant ...of Concern (VOC). The genome of the Omicron VOC contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and potential to evade immune responses developed for previous VOCs such as Alpha and Delta. In the days since the designation of B.1.1.529 as a VOC, infections with the lineage have been reported in countries around the globe and many countries have implemented travel restrictions and increased border controls in response. We putatively detected the Omicron variant in an aircraft wastewater sample from a flight arriving to Darwin, Australia from Johannesburg, South Africa on the 25th of November 2021 via positive results on the CDC N1, CDC N2, and del(69–70) RT-qPCR assays per guidance from the WHO. The Australian Northern Territory Health Department detected one passenger onboard the flight who was infected with SARS-CoV-2, which was determined to be the Omicron VOC by sequencing of a nasopharyngeal swab sample. Subsequent sequencing of the aircraft wastewater sample using the ARTIC V3 protocol with Nanopore and ATOPlex confirmed the presence of the Omicron variant with a consensus genome that clustered with the B.1.1.529 BA.1 sub-lineage. Our detection and confirmation of a single onboard Omicron infection via aircraft wastewater further bolsters the important role that aircraft wastewater can play as an independent and unintrusive surveillance point for infectious diseases, particularly coronavirus disease 2019.
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•First detection of SARS-CoV-2 Omicron VOC in aircraft wastewater samples•Sequencing of the aircraft wastewater sample confirmed the presence of the Omicron VOC.•Omicron VOC consensus genome clustered with the B.1.1.529 BA.1 sub-lineage.•Analytical detection of Omicron in wastewater corroborated with a single onboard infection
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